FDA Grants Priority Review to Huntington Disease Gene Therapy BLA

The FDA has accepted uniQure's biologics license application (BLA) for ifezuntirgene inilparvovec (AMT-130), an investigational gene therapy for Huntington disease, and granted it Priority Review. The agency set a target action date of May 1, 2027, under the Prescription Drug User Fee Act (PDUFA), and said it is tentatively planning to hold an advisory committee meeting, though no date has been finalized.¹

The BLA was submitted under the accelerated approval pathway. Matt Kapusta, chief executive officer of uniQure, said the acceptance “marks an important milestone for the Huntington's disease community, which has waited generations for a treatment that changes the course of this devastating disease.” He added that the company, “backed by compelling data from our Phase I/II studies," believes ifezuntirgene inilparvovec “has the potential to become the first disease modifying treatment for Huntington's disease.”¹

Ifezuntirgene inilparvovec uses uniQure's gene-silencing miQURE platform to deliver a microRNA designed to silence the huntingtin gene and the toxic exon 1 protein fragment it produces. It is given as a single administration through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum. The therapy holds Breakthrough Therapy, RMAT (Regenerative Medicine Advanced Therapy), and Fast Track designations; it is the first Huntington disease candidate to hold both Breakthrough Therapy and RMAT status.

Huntington disease is an inherited, autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene, affecting an estimated 75,000 people across the US, EU, and UK. No approved therapy currently delays its onset or slows its progression.^1,2

READ MORE: SKY-0515 Shows Sustained Benefit at 15 Months in Huntington Disease

The BLA is based on 51 patients treated across uniQure's Phase I/II program: a US randomized study (26 patients: 6 low dose, 10 high dose, 10 sham, with 4 sham patients later crossing over to treatment), a European open-label study (13 patients: 6 low dose, 7 high dose), a third cohort of 12 patients exploring both doses with immunosuppression, and a fourth cohort of 6 patients receiving the high dose who had lower striatal volumes than earlier cohorts.

As part of the accelerated approval requirement, uniQure has agreed with the FDA on a confirmatory trial of about 200 patients, randomized 2:1 to ifezuntirgene inilparvovec or standard of care, with Total Functional Capacity (TFC) at 36 months as the primary endpoint. Screening in the US is planned to begin by the end of 2026.¹

A regulatory path that reversed before reaching acceptance

uniQure first reported safety data from the program in December 2021, when the first 4 patients, 2 treated and 2 who underwent sham surgery, had reached 1 year of follow-up. The company reported no serious adverse events related to the low-dose (6x10¹² vg) treatment, along with a transient rise in cerebrospinal fluid neurofilament light chain (NfL) that returned to baseline in the treated patients.³

Jody Corey-Bloom, MD, PhD, professor of neurosciences at the University of California, San Diego and chairperson of the trial's Data Safety Monitoring Board, said at the time that AMT-130 “appears to be generally well tolerated both immediately after surgical administration and at one year of follow up in these four patients.”³

By December 2024, following an RMAT Type B meeting with the FDA, uniQure announced the agency had agreed that data from the ongoing Phase I/II studies, compared against an external natural history control, could serve as the primary basis for a BLA under the accelerated approval pathway, without an additional presubmission study. The FDA also agreed that the composite Unified Huntington's Disease Rating Scale (cUHDRS) could serve as an intermediate clinical endpoint, with CSF NfL reductions as supportive evidence.⁴

uniQure reported positive topline results from the 36-month analysis in September 2025. In the high-dose group, cUHDRS, the trial's primary endpoint, showed 75% slowing of progression relative to a propensity score-matched external control drawn from the Enroll-HD natural history dataset (P =.003), and TFC showed a 60% difference (P =.033). Results on the Symbol Digit Modalities Test (88% slowing, P=.057) and Total Motor Score (59% slowing, P =.1741) were described by the company as favorable trends rather than statistically significant findings; the Stroop Word Reading Test showed 113% slowing (P =.0021). Mean CSF NfL was 8.2% below baseline at 36 months.⁵

Sarah Tabrizi, MD, FRCP, FRS, FMedSci, PhD, professor of clinical neurology and director of the University College London Huntington's Disease Centre, called the findings significant, saying they were “the most convincing in the field to date” and “underscore potential disease-modifying effects in Huntington's disease.”⁵

In a June 2026 update, uniQure said the FDA had confirmed that the 36-month Phase I/II analysis would be acceptable as the primary basis for a BLA, and the company said it intended to submit the application in the third quarter of 2026. That update also noted the FDA sought to align on the confirmatory study's design before submission, including whether to use a concurrent standard-of-care control instead of a sham procedure.⁶

Roughly 5 months earlier, in a November 2025 disclosure, uniQure said the FDA had reversed its position, telling the company that the Phase I/II program data, even against the external control, “will not be enough to support an approval filing at this time,” a shift uniQure characterized as a departure from the agency's November 2024 guidance. That update prompted uniQure to re-engage with the FDA on a path forward before the regulatory alignment described in its June 2026 update.⁷

uniQure formally submitted the BLA in September 2026, citing additional 2026 data presented at the American Academy of Neurology Annual Meeting, including continued cUHDRS slowing and no new long-term safety concerns through 3 years of follow-up.⁸

Pipeline context: AMT-260 in epilepsy

uniQure's gene therapy platform also underlies AMT-260, an unrelated program using an AAV9 vector to suppress GRIK2 in the hippocampus, in development for refractory mesial temporal lobe epilepsy. In a first cohort update in June 2026, the company reported that 3 of 6 low-dose patients had seizure reductions of 79% to 100% from baseline at months 4 through 6, with no serious adverse events related to treatment or the surgical procedure.⁹

Walid Abi-Saab, MD, chief medical officer of uniQure, said the data “provide preliminary evidence of biological activity of AMT-260,” while cautioning that the findings were based on a limited number of patients.⁹

REFERENCES
1. uniQure announces FDA acceptance and priority review of the Biologics License Application for ifezuntirgene inilparvovec for the treatment of Huntington's disease. News release. uniQure. Published November 2, 2026. Accessed November 2, 2026. https://www.biospace.com/press-releases/uniqure-announces-fda-acceptance-and-priority-review-of-the-biologics-license-application-for-ifezuntirgene-inilparvovec-for-the-treatment-of-huntingtons-disease
2. Yohrling G, Raimundo K, Crowell V, Lovecky D, Vetter L, Seeberger L. Prevalence of Huntington's disease in the US. Neurology. 2020;94(15 Suppl):954. doi:10.1212/WNL.94.15_supplement.954
3. uniQure announces clinical update on first patients in Phase I/II clinical trial of AMT-130 gene therapy for the treatment of Huntington's disease. News release. uniQure. Published December 16, 2021. Accessed November 2, 2026. https://www.biospace.com/article/releases/uniqure-announces-clinical-update-on-first-patients-in-phase-i-ii-clinical-trial-of-amt-130-gene-therapy-for-the-treatment-of-huntington-s-disease/
4. uniQure announces alignment with FDA on key elements of accelerated approval pathway for AMT-130 in Huntington's disease. News release. uniQure. Published December 10, 2024. Accessed November 2, 2026. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-alignment-fda-key-elements-accelerated
5. uniQure announces positive topline results from pivotal Phase I/II study of AMT-130 in patients with Huntington's disease. News release. uniQure. Published September 24, 2025. Accessed November 2, 2026. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-topline-results-pivotal-phase-iii
6. uniQure announces plan for BLA submission for AMT-130 in Huntington's disease. News release. uniQure. Published June 17, 2026. Accessed November 2, 2026. https://uniqure.gcs-web.com/node/12796
7. uniQure provides regulatory update on AMT-130 for Huntington's disease. News release. uniQure. Published November 3, 2025. Accessed November 2, 2026. https://www.globenewswire.com/news-release/2025/11/03/3179114/0/en/uniQure-Provides-Regulatory-Update-on-AMT-130-for-Huntington-s-Disease.html
8. uniQure announces submission of Biologics License Application for ifezuntirgene inilparvovec (AMT-130) in Huntington's disease. News release. uniQure. Published September 2, 2026. Accessed November 2, 2026. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-submission-biologics-license-application
9. uniQure announces preliminary data on the first cohort in the Phase I/IIa clinical trial of AMT-260 in refractory mesial temporal lobe epilepsy. News release. uniQure. Published June 19, 2026. Accessed November 2, 2026. https://uniqure.gcs-web.com/node/12836